eukaryotic translation initiation factor 2-alpha kinase 3; PRKR-like endoplasmic reticulum kinase; pancreatic eIF2-alpha kinase; HsPEK (EIF2AK3, PEK, PERK)

Function

• phosphorylates alpha subunit of eukaryotic translation- initiation factor 2 (eIF2)
  • results in inactivation of eIF2
  • rapid reduction of translational initiation
  • repression of global protein synthesis
• effector of unfolded protein response
• induces G1 growth arrest due to the loss of cyclin D1
• forms dimers with HSPA5/BIP in resting cells
• dissociates from HSPA5/BIP & oligomerizes in ER-stressed cells
• interacts with DNAJC3
• autophosphorylated

Structure

• N-glycosylated
• the lumenal domain senses perturbations in protein folding in the ER, probably through reversible interaction with HSPA5/BIP
• belongs to the protein kinase superfamily, Ser/Thr protein kinase family, GCN2 subfamily
• contains 1 protein kinase domain

Compartment

endoplasmic reticulum

Expression

• ubiquitous
• induction by ER stress

Pathology

• defects are the cause of Wolcott-Rallison syndrome
• PERK is activated in the hippocampus of Alzheimer's disease patients & in the pons & medulla of patients with progressive supranuclear palsy
  • degree of PERK activation seems to be correlated with both age & tau pathology but not with A-beta plaque burden

Comparative biology

• in mice, PERK promotes misfolding and halts synthesis of specific proteins
• inhibitor of PERK halts progression of prion disease in mice, but does not reverse deficits
• inhibition of PERK or reduced expression of PERK improves long-term memory & behavioral plasticity in rats*

More general terms

• serine/threonine kinase
• glycoprotein
• membrane protein

Database

• OMIM: https://mirror.omim.org/entry/226980
• OMIM: https://mirror.omim.org/entry/604032
• UniProt: http://www.uniprot.org/uniprot/Q9NZJ5.html